BETHESDA, Md. (August 30, 2005) - Even the U.S. National Institutes of Health doesn't know what causes gastroesophageal reflux disease, or GERD. And NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) says there's an unclear relationship between GERD, heartburn and hiatal hernia (HH). Patients may have only one out of three, any two out of three, or all three.

Nevertheless, clinicians know that all three often occur together and that a variety of lifestyle changes, medication, surgery and recently approved devices and an implant are imperfect solutions.

An encounter between a Taiwanese gastroenterologist wanting to study acupuncture and an opening at the Royal Adelaide Hospital resulted in two experiments looking into how the traditional Eastern approach might affect transient lower esophageal sphincter relaxations (TLESRs). Since TLESRs are "the most important mechanism of acid reflux in normal subjects and patients with GERD," they were targeted for study.

The paper describing the study, "Inhibition of transient lower esophageal sphincter relaxations by electrical acupoint stimulation," appears in the August issue of the American Journal of Physiology-Gastrointestinal and Liver Physiology, published by the American Physiological Society. Research was performed by Duowu Zou, Wei Hao Chen, Katsuhiko Iwakiri, Rachael Rigda, Marcus Tippett and Richard H. Holloway of the Royal Adelaide Hospital, Australia.

The Neiguan connection

"It was an out-of-left-field approach, without any real expectations that it might work," according to Richard H. Holloway, in whose Royal Adelaide Hospital laboratory the work was done, "but we had well-defined technology and measurements for studying GERD." The protocol utilized electrical acupoint stimulation, a high-tech type of acupuncture, with a GERD model imposed on normal subjects by inflating a balloon in their stomachs.

In two separate studies, barely perceptible stimulation was applied at the acupoint known as Neiguan on the wrist. "This reduced TLESRs by a very significant 40% -- from six an hour to 3.5 an hour," Holloway said. The paper added: that the rate of TLESRs during the Neiguan acupoint stimulation "was significantly lower than that during both the baseline period without any stimulation (six per hour, with a range of five to eight), and the period of sham stimulation at the hip (six per hour; range: four to eight) with a probability value of less than 0.02."

The paper noted that "because gastric distension is the major trigger for TLESRs, Neiguan appeared to be a more relevant site for affecting triggering of TLESRs than did Hukoau," another gastrointestinal-related acupuncture site.

Mechanisms of action elusive; role of opioids discounted

Addressing the mechanisms of action, the paper said: "Whether gastric distension triggers TLESRs through tension or stretch receptors remains controversial. Nevertheless, because the distension volume [in the experiments] was kept constant and because acupoint stimulation did not affect gastric pressure, it seems unlikely that it was acting through alterations in gastric motility. The mechanism of inhibitory effect of electric acupoint stimulation on triggering of TLESRs thus remains to be elucidated."

Indeed, from a scientific viewpoint, the entire question of how acupuncture works is still a matter of much conjecture, though some studies have suggested that opioid receptors may be involved. So after the initial findings, the Holloway team essentially repeated the experiment to test this hypothesis by seeing if the receptor antagonist naloxone would block the acupoint effect. The results were negative, "but due to the peculiarity of results in a four-way study, we can't be sure that opioids aren't involved," Holloway said.

Holloway added: "What we've shown here is a rather interesting proof of concept, which tackles one of the approaches to acid reflux by controlling the valve that controls acid leak. If we can stop the TSLERs events, that would be a major therapeutic gain. But it's a major leap from where we are to a real cure," he said.

Next steps

Holloway said that studying the effect of acupoint on healthy subjects in the context of eating a meal, rather than mechanically distending the stomach, would be useful.

The paper concludes: "The efficacy of electric acupuncture in reducing the frequency of TLESRs and reflux in patients with GERD...awaits further study.

"In addition, knowledge of the underlying mechanisms of the effect of electric acupuncture may help to identify target sites for therapeutic intervention on TLESRs."

The GERD-HH connection, and the question of a possible protective role of H. pylori

Two areas of additional interest in this area concern the GERD-HH connection and H. Pylori.
"The possible role of a hiatal hernia in GERD has literally gone full circle," Holloway noted. Initially the hiatus hernia was thought to be the major, perhaps only pathogenetic factor for reflux as it was the only abnormality that could be detected in patients with reflux symptoms; endoscopy and esophageal manometry had yet to be invented. With the development of esophageal manometry, the presence and importance of the LES was recognized, and abnormal LES function in reflux disease was identified. Consequently, the importance of hiatus hernia was virtually dismissed.

"Subsequent research, however, has clearly shown that the development of a hiatus hernia has a detrimental effect on LES function. Thus reflux disease occurs because of LES dysfunction and, in many patients, the additional effects of a hiatus hernia," Holloway said.

As for H. pylori, in a fact sheet on heartburn, HH and GERD, NIDDK includes these poignant observations: "Much research is needed into the role of the bacterium Helicobacter pylori. Our ability to eliminate H. pylori has been responsible for reduced rates of peptic ulcer disease and some gastric cancers. At the same time, GERD, Barrett's esophagus, and cancers of the esophagus have increased. Researchers wonder whether having H. pylori helps prevent GERD and other diseases. Future treatment will be greatly affected by the results of this research," the NIDDK paper concludes.

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Source

The study, "Inhibition of transient lower esophageal sphincter relaxations by electrical acupoint stimulation," appears in the August issue of the American Journal of Physiology-Gastrointestinal and Liver Physiology, published by the American Physiological Society. Research was performed by Duowu Zou, Wei Hao Chen, Katsuhiko Iwakiri, Rachael Rigda, Marcus Tippett and Richard H. Holloway of the Department of Gastroenterology, Hepatology, and General Medicine, Royal Adelaide Hospital; Holloway also is at the Dept. of Medicine, University of Adelaide, South Australia, Australia.

Editor's note: The media may obtain electronic versions of Zou et al. and interview members of the research team by contacting Mayer Resnick at the American Physiological Society, 301.634.7209, cell 301.332.4402 or mresnick@the-aps.org.

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